The OVERALL OBJECTIVE of this proposal is to integrate the anatomic and physiologic information derived from computed tomographic angiograms for the precise identification of coronary artery lesions that cause ischemia. This proposal is a companion study to ISCHEMIA Trial. For patients with stable ischemic heart disease, myocardial ischemia may arise as a consequence of obstructive coronary artery disease (CAD) and is useful for guiding decisions of revascularization. To date, non-invasive stress tests have served as a mainstay for identifying ischemia; these tests include echocardiography, magnetic resonance and myocardial perfusion scintigraphy (MPS). Among these, MPS is performed most commonly due to its ability to identify obstructive CAD, reclassify CAD likelihood, and predict adverse events. CT has emerged as a non-invasive method that permits direct visualization of CAD, demonstrates high performance for obstructive CAD compared to invasive coronary angiography (ICA), and predicts adverse prognosis. Beyond stenosis, CT enables evaluation of additional atherosclerotic plaque characteristics (APCs) that demonstrate high agreement to invasive methods and may augment determination of coronary lesions that cause ischemia. Recent developments in CT also permit physiologic assessment of CAD by applying computational fluid dynamics to typically- acquired CT scans for calculation of coronary artery pressure and flow, thus enabling the non-invasive calculation of fractional flow reserve (FFRCT), a measure of vessel-specific ischemia. The OVERALL HYPOTHESIS of this proposal is that integrating anatomic APCs with physiologic FFRCT will optimize identification of coronary lesions that are ischemia-causing. We propose 3 specific aims: AIM 1: To assess performance of anatomic APCs by CT for diagnosis of vessel-specific ischemia. AIM 2: To assess performance of physiologic FFRCT for diagnosis of vessel-specific ischemia. AIM 3: To directly compare an integrated anatomic-physiologic (APC-FFRCT) CT measure to MPS for diagnosis of lesion-specific ischemia. The work in this proposal will provide the rationale for a novel diagnostic paradigm that is more accurate than conventional stress imaging testing for identifying patients who manifest ischemia and pinpointing the coronary lesions that are the cause; thus, allowing for better selection of individuals for revascularization and eliminating unnecessary invasive procedures.